Neonatal Lung Disease: Mechanisms Driving Sex Differences

Lingappan, Krithika; Hayward-Piatkovskyi, Brielle; Gleghorn, Jason P.

doi:10.1007/978-3-030-63549-7_5

Cited by 6 publications

(3 citation statements)

References 167 publications

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“…This multicellular interaction is an example of sender-receiver type signaling, where morphogen secretion from one cell type induces a response from another cell type. Often deviations in the strength or positioning of morphogen concentrations and gradients regulate this intercellular interaction and underpin developmental diseases and congenital birth defects [11][12][13][14][15][16]. Since these interactions function at the multicellular level (tissue scale) with spatial heterogeneity, many traditional methods of inferring the gene regulatory networks that comprise these interactions are insufficient.…”

Section: Introductionmentioning

confidence: 99%

Methodology for inference of intercellular gene interactions

Modi

Zurakowski

Gleghorn

2023

Preprint

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To govern organ size, shape, and function, cell-secreted diffusible molecules called morphogens spatially pattern cell differentiation, gene expression, and proliferation. Local morphogen concentration governs cell differentiation through gene regulatory networks (GRN). Previous inference methodologies tackle intercellular GRN inference between cells of one type. This is insufficient, as many developmental systems consist of cells of different types interacting with each other. Inference methodologies of GRNs between different cell types assume knowledge of diffusible morphogen identity and concentration. This makes their applicability limited in real biological systems. Here, we develop a computational methodology to infer the intercellular GRN derived from experiments that use fluorescence from reporter proteins for gene expression measurements. For validation, we demonstrate the methodologyin silicousing three case studies based on developmental and synthetic biology. The results show that, barring practical identifiability limitations, the methodology successfully infers the intercellular GRNs.

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Section: Introductionmentioning

confidence: 99%

Methodology for inference of intercellular gene interactions

Modi

Zurakowski

Gleghorn

2023

Preprint

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“…Advances in neonatal care have altered the epidemiology of extreme prematurity over the past years with more infants born at 22 and 23 weeks of gestation surviving to reach 36 weeks of postmenstrual age, when they are diagnosed with BPD 3–5 . It is possible that the mechanisms driving sex differences in neonatal lung disease have not been adequately expressed at a gestation that corresponds to the new border of viability, and gender differences are thus less pronounced in these very low gestations 6 . Although some studies have reported an absence of male disadvantage in infants below 25 weeks of gestation, these reports originated from cohorts of moderate size and included a relatively limited number of infants below 24 weeks of gestation 7,8 …”

Section: Introductionmentioning

confidence: 99%

“…lung disease have not been adequately expressed at a gestation that corresponds to the new border of viability, and gender differences are thus less pronounced in these very low gestations. 6 Although some studies have reported an absence of male disadvantage in infants below 25 weeks of gestation, these reports originated from cohorts of moderate size and included a relatively limited number of infants below 24 weeks of gestation. 7,8 In this study, we aimed to use the whole population of extreme preterm infants born in England in a recent 5-year period to explore whether the male disadvantage in mortality and respiratory morbidity was present in infants born at 22 and 23 weeks of gestation.…”

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confidence: 99%

Sex differences in preterm respiratory morbidity: A recent whole‐population study

Dassios,

Harris,

Williams

et al. 2023

Acta Paediatrica

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AimTo determine whether there were differences between male and female infants in respiratory morbidity in a whole population of extremely preterm infants, including infants born below 24 weeks of gestation.MethodsRetrospective whole‐population study of all infants <28 weeks of gestation admitted to a neonatal unit in England from 2014 to 2019. Bronchopulmonary dysplasia (BPD) development was defined as any respiratory support at 36 weeks postmenstrual age.ResultsThe 11 844 infants had a median (IQR) gestational age of 26.0 (24.9–27.1) weeks and a birth weight of 0.81 (0.67–0.96) kg. The duration of invasive ventilation was longer in male compared to female infants who were born at 24–27 completed weeks of gestation (p < 0.001), but not significantly different between male and female infants born at 22 and 23 weeks of gestation (p = 0.446). The incidence of BPD was higher in male compared to female infants born at 24–27 weeks of gestation (p < 0.001) but not different between male and female infants born at 22 and 23 weeks of gestation (p = 0.148).ConclusionRespiratory morbidity was more pronounced in male compared to female extremely preterms, only in gestations 24–27 completed weeks. Male predominance was absent in infants born below 24 weeks of gestation.

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Lung Development in a Dish: Models to Interrogate the Cellular Niche and the Role of Mechanical Forces in Development

Chernokal,

Gonyea,

Gleghorn

2023

Advances in Experimental Medicine and Biology

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Over the past decade, emphasis has been placed on recapitulating in vitro the architecture and multicellular interactions found in organs in vivo [1, 2]. Whereas traditional reductionist approaches to in vitro models enable teasing apart the precise signaling pathways, cellular interactions, and response to biochemical and biophysical cues, model systems that incorporate higher complexity are needed to ask questions about physiology and morphogenesis at the tissue scale. Significant advancements have been made in establishing in vitro models of lung development to understand cell-fate specification, gene regulatory networks, sexual dimorphism, three-dimensional organization, and how mechanical forces interact to drive lung organogenesis [3–5]. In this chapter, we highlight recent advances in the rapid development of various lung organoids, organ-on-a-chip models, and whole lung ex vivo explant models currently used to dissect the roles of these cellular signals and mechanical cues in lung development and potential avenues for future investigation (Fig. 3.1).

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Neonatal Lung Disease: Mechanisms Driving Sex Differences

Cited by 6 publications

References 167 publications

Methodology for inference of intercellular gene interactions

Methodology for inference of intercellular gene interactions

Sex differences in preterm respiratory morbidity: A recent whole‐population study

Lung Development in a Dish: Models to Interrogate the Cellular Niche and the Role of Mechanical Forces in Development

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